Azemiglitazone

Azemiglitazone (MSDC-0602) is an orally active thiazolidinedione (TZD) -like molecule, which binds to PPARγ with low binding and activating affinity. Azemiglitazone inhibits mitochondrial pyruvate carrier (MPC), which inhibits Alzheimer’s disease and diminishes nonalcoholic steatohepatitis (NASH) caused liver injury[4][5].

[1]Chen Z, et al. Resistance and metabolic derangements in obese mice are ameliorated by a novel peroxisome proliferator-activated receptor γ-sparing thiazolidinedione. J Biol Chem. 2012 Jul 6;287(28):23537-48.|[2]Vigueira PA, et al. The beneficial metabolic effects of sensitizers are not attenuated by mitochondrial pyruvate carrier 2 hypomorphism. Exp Physiol. 2017 Aug 1;102(8):985-999.|[3]McCommis KS, et al., Loss of Mitochondrial Pyruvate Carrier 2 in the Liver Leads to Defects in Gluconeogenesis and Compensation via Pyruvate-Alanine Cycling. Cell Metab. 2015 Oct 6;22(4):682-94.|[4]McCommis KS, et al., Targeting the mitochondrial pyruvate carrier attenuates fibrosis in a mouse model of nonalcoholic steatohepatitis. Hepatology. 2017 May;65(5):1543-1556.|[5]Phelix, C., et al., MSDC-0160 and MSDC-0602 binding with human mitochondrial pyruvate carrier (MPC) 1 and 2 heterodimer: PPARγ activating and sparing TZDs as therapeutics. Int. J. Knowl. Knowl. Bioinform.2017, 7, 43–67.|[6]Chen Z, et al., Insulin resistance and metabolic derangements in obese mice are ameliorated by a novel peroxisome proliferator-activated receptor γ-sparing thiazolidinedione. J Biol Chem. 2012 Jul 6;287(28):23537-48.